Packed columns for chromatography



1966 I. HALASZ ETAL 3,283,483

PACKED COLUMNS FOR CHROMATOGRAPHY Filed March 11, 1965 V 2 Sheets-Sheet1 .12 l4 DETECTOR CARRIER PRESSURE SAMPLE GAS HREGLLATOR INJECTOR*EXHAUST l l /6 FIG. I 1 2O RECORDER g 7 se INVENTORS ISTVAN HAL'ASZ BYERWIN HEINE MZQW ATTORNEY FIG.

l. HALASZ ETAL PACKED COLUMNS FOR CHROMATOGRAPHY 2 34 5 6% 9lOl||2| 3|4|5 Nov. 8, 1966 Filed March 11, 1965 FIG.

INVENTORS ISTVAN HAL'ASZ BY ERWIN HEINE SEC.

United States Patent 3,283,483 PACKED COLUMNS FOR CHROMATOGRAPHY IstvanHalasz, Frankfurt am Main, Germany, and Erwin Heine, Riverside, Calif.,assignors to Beckman Instruments, Inc., a corporation of CaliforniaFiled Mar. 11, 1965, Ser. No. 439,008 Claims priority, applicationGermany, May 4, 1962, H 45,689; Mar. 19, 1964, H 52,097 9 Claims. '(Cl.55386) The present invention relates to separation columns for use inchromatographic analysis apparatus and more particularly to columnpacking structure adapted to promote high-speed separation of thecomponents of a fluid sample and to the method of making such columns.

This application is a continuation-in-part of our now abandonedcopending application entitled Packed Columns for Gas Chromatography,filed April 23, 1963, Serial No. 275,134 and assigned to the assignee ofthe present invention.

In chromatographic analysis, a small sample in the form of a gas orliquid mixture is introduced into a suitable fluid carrier stream andcarried by the stream through a separation column. The separation columnis normally a tubular conduit packed with a material for which each ofthe respective components of the sample mixture has its own uniqueaffinity or retention time. The difference in the affinity or retentiontime of the respective components of the mixture causes the differentcomponents of the sample to stay within the column for different lengthsof time. Therefore, the components of the mixture emerge from the columnat different times. The affinity of most liquid and gaseous compoundsfor various packing materials is well known and the order of emergenceof the individual components of a sample mixture can be easilyascertained.

As each component emerges from the column, it is passed through adetector device which measures a physical or electrical property of therespective component against a reference property of the carrier fluid.The output of the detector is representative of the percentage orquantity of the particular component within the sample. A recording ofthe output of the detector for a particular liquid or gaseous sampleresults in a multi-peaked curve, wherein each peak may represent onecomponent of the sample. The quantity of each of the components isrepresented by the area under its respective portion of the curve andmay be calculated by integration or, in some cases, may be estimatedfrom the peak height.

The material causing the separation of the respective liquid or gaseouscomponents of a sample is commonly called the stationary phase of thecolumn. Separation is obtained either because the stationary phase hasadsorbing surfaces or because the surface has been coated with a thinfilm of partitioning liquid, having a high boiling point and for whichthe liquid or gaseous constituents of the sample have an aflim'ty."

Typical packed columns presently in use in gas chromatography analysisapparatus have an inner diameter of about 1.5-6 mm. and are packed withparticles having extremely small size. It was believed necessary in thepast, in order to obtain good separation or resolution with a minimumamount of spreading of the sample during flow through the column, tofill the column as homogeneously and as densely as possible by suchmeasures as vibrating and knocking the column. This was done to make theflow of the sample through the column follow a uniform frontaldisplacement pattern along the length of the column. A great amount ofdata has been published in the gas chromatography field tending to showthat peak spreading expressed in terms of height equivalent to atheoretical plate (plate height or H.E.T.P.), in-

creases essentially linearly with increasing particle diameter as usedwith the columns normally employed. It has also been stated and believedthat adverse effects result from the non-uniformity of packing whichoccurs when particles of diameter greater than 5 to /s the insidediameter of the column are used. It has thus been the universal beliefthat the particles or grainsof packing material shoud be of uniformdimensions and extremely small in size. Thus, prior art or classicalchromatographic columns, employed in both liquid or gas chromatography,have always been packed with particles of a size less than of the tubeinside diameter and usually of a magnitude very much smaller in order topromote as dense a packing as possible and thereby preventcrosssectional variations in the flow velocity of the sample as ittraverses the length of the column.

Such columns have a high resistance to flow and columns havingsuflicient length to perform difiicult separations require extremelyhigh inlet pressures. Thus, the speed of analysis with such columns islimited by the high pressure required to obtain high linear gasvelocity. Even with relatively short, densely packed columns, high inletpressure is necessary to obtain reasonable speeds of analysis. However,the amount of pressure that may be used to attain greater speed ofanalysis has its limitations. A practical upper limit on the pressurepermissible at the column inlet is set by the requirement forintroducing samples at this point through a hermetically sealedinjection means.

In the past, the use of packed columns having diameters smaller thanabout 1.5 mm. has proved impractical because of the excessive pressuredrop occurring when such a column is densely packed with particles inthe size range considered necessary. For this reason, and additionallybecause of the great difficulty encountered in uniformly packing smalldiameter columns,.it was heretofore believed that the lower limit fordiameters of packed chromatograph columns was about 1.5 mm.

Columns having smaller diameters than 1.5 mm. have been used in gaschromatographic analysis but these have not been columns packed with aparticulate type separation material. Rather, these columns are ofopentubular type, and have the inner surface thereof coated with aseparating liquid phase. The above-described open-tubular column isdisclosed in United States Patent No. 2,920,478 which issued to M. J. E.Golay on January 12, 1960. While the open-tubular column is useful forsome purposes and does increase the speed of analysis in thoseapplications to which it may be applied, it does have its limitations.Only the liquid phase or partitioning liquid of the column acts in theseparation and such columns are very limited in the amount of liquidphase which they can contain. This limits the usefulness of such columnsto extremely small sample sizes and to components having strong affinityfor the liquid phase employed. For example, open-tubular columns havefound application in the gas chromatograph analysis of mixtures of highboiling point hydrocarbons although such columns are impractical forseparation of mixtures of the lighter hydrocarbon gases such as methane,ethane, propane and butane. It has been suggested that the samplecapacity of open-tubular columns and their usefulness for less stronglyretained components may be improved by making the inner surface thereofrough or by coating the inner surface with a very finely granulatedpowder.

While it is true that the relative size and uniformity of the particlesor grains of packing material probably do have a direct relationship tothe amount of spreading that occurs in a gas sample during fiow througha column packed with particles that are extremely small in grains isgreater than As of the inner diameter of the column. Using thisapproach, packed columns of relatively low pressure drop can beconstructed having greatly increased speed of operation with minimumdecrease in resolution due to the spreading effect of the column on thesample components.

Accordingly, it is an object of the present invention to provide a newand improved chromatographic column having a packing structure adaptedto greatly increase the speed of separation within the column withmrnrmum loss of resolution due to spreading within the column.

Another object of the present invention is to provide an improved packedchromatograph column having an extremely high permeability (andconsequent lowpressure drop) and correspondingly high speed ofseparation for a particular resolution as compared to known types ofpacked columns presently used in the field.

A further object of the present invention is to provide a method ofmaking extremely small diameter (less than {1 mm.) packed chromatographcolumns. Further objects and advantages of the invention will becomeapparent as the following description proceeds, and the features ofnovelty which characterize the inyention will be pointed out withparticularity in the claims annexed to and forming a part of thisspecification. Briefly, the present inventioncomprises a separationcolumn packed with a solid particulate or granular material, with thegrains of packing material having a crosssectional dimension greaterthan /5 of the inner diameter of the column. In a preferred embodimentof the invention, the inner diameter of the column is less than 1 mm.and, in contrast to the traditional packing concepts, the granularpacking particles are of a dimension sufficiently large to assure thatthe inter-particle void space within the column is at least 45 percentof the total volume of the column that is packed. Within the specifiedrange of ratio of particle diameter to column diameter, suchinter-particle void volume rises naturally as the particles pack intothe column in contact with and supporting one another.

Another aspect of the present invention is a method for constructingsmall diameter packed chromatographic columns incorporating the steps ofpacking a small diameter column with a particulate or granular packingmaterial having a dimension greater than /s of the inner diameter of thecolumn ultimately to be formed, and

supporting the particles during the packing thereof to pro- ,vide aninter-particle void within the packed portion of the column that is atleast 45 percent of the total volume of the packed portion of the columnand then drawing the column down to the desired diameter of 2 mm. or

less.

For a better understanding of-the invention, reference :may be had tothe accompanying drawings in which:

the process of drawing down a packed tube through a die;

FIG. 5 is a greatly magnified illustration of a packed glass tube whichhas been drawn down to a diameter of less than 1 mm.;

FIG. 6 is a schematic cross-sectional view showing a tubular conduitpacked around a rod inserted in the conduit in accordance with oneembodiment of the invention;

FIG. 7 is a cross-sectional view of the column of FIG. 6 taken alongline 77; and

FIG. 8 is a curve plotted from test data illustrating one measure ofcolumn performance plotted against the tube diameter to particlediameter ratio.

Referring now to the drawings, FIG. 1, represents a typical arrangementfor a gas chromatograph system including a pressure regulator or flowcontroller 12, a sample injector 14, a chromatograph column 16, adetector 18 and a recorder 20. The flow of carrier gas, ordinarilyhelium, although other gases such as argon, nitrogen,-

carbon dioxide, hydrogen and. even air may be used, is controlled by thepressure regulator 12. At a particular time a quantity of sample isinjected into the carrier gas by means of the sample injector 14 andcomponents ofthe sample are separated as the sample moves through thecol-.

umn 16. The detector 18 provides an output indicating the presence of asample component in the column efiluent.

As pointed out previously, the output of the detector may be used as aquantitative measure of the com-ponentsof the sample. In actualpractice, the output of the detector is ordinarily recorded in some formfor subsequent review,

although the output may merely be indicated for contemporaneous visualinspection.

While the apparatus of FIG. 1 is a typical gas chromatograph analysissystem, it will be understood that the chromatograph column structure ofthe present inven-' tion is adapted for use in liquid chromatographsystems as well as for use in gas chromatograph systems. In a liquidchromatograph system, a carrier solution of liquid,

such as a solution of ethyl alcohol, or a solution of pyridine, butanoland water, is pumped through the system under pressure in place of thecarrier gas stream. In a liquid chromatograph system, the sample isinjected into the liquid carrier stream by means of a sample injectorcorresponding to the sample injector 14 of FIG. 1 that preferablyinjects the sample mixture in liquid form. The

sample mixture is then carried by the liquid carrier solutron throughthe chromatograph column for separation into its various components. Theonly major difference in a liquid chromatograph system over a gaschromatograph of the peak or may be estimated from the height of thepeak. This latter method, i.e., estimating from peak height, is adesirable method of analysis and is preferable where the analysis mustbe performed very quickly and on a very extensive or frequentlyrepetitive basis as in chemical process control. It will be understoodthat this method 1s only accurate where the peak heightsarerepresentative of the proportionate quantities of the individualcomponents of the sample mixture. When the peaks so formed aresufiiciently sharp and narrow to permit essentially complete resolutionor separation of the individual sample components, then peak heights areusually fairly representative of the proportionate quantity of theparticular components present. However, when the sample spreads as 1tflows through the column 16, the respective components of the sample donot emerge from the column as narrow bands of the particular separatedcomponent, but tend to spread and emerge from the column in relativelywide bands which may overlap for successive components. This results ina curve or output from the detector in which the representative portionsof the curve are not sharply distinguished peaks but are smooth,relatively wide curves in which an individual peak height cannot beconsidered, on a uniform basis, as being representative of theparticular quantity of a single component in the sample. Thus, it isdesirable to prevent spreading as much as possible in order to obtaingood resolution or separation of the particular components of thesample. This requires a column which produces as little spreading aspossible, yet contains sufficient partitioning agent to provideseparation of the components from one another.

Referring now to FIG. 2, there is shown a greatly enlarged view of thechromatographic column 16 which is designed to obtain good resolution orseparation of the components of a sample in an extremely short time witha minimum of spreading of the fluid sample as it flows through thecolumn. The column 16 comprises a tubular conduit 22 which is filled orpacked with numerous particles 24 made from aluminum oxide or otherwell-known packing material. In the embodiment shown in FIG. 2, theparticles are granular in character and have a major dimension that isabout /3 to of the inner diameter of the tube 22. The size of theparticles and their number is such that they comprise not more than 55percent of the inner volume of the packed portion of the tube.

A separating column having such large particles or grains in comparisonto the tube diameter provides, contrary to established belief in thefield, excellent separating powers especially for sample mixtures havinga low boiling point. The column can be operated with a considerablylower carrier pressure to obtain extremely high linear speed of thecarrier stream as compared to traditional columns having densely packedparticles of extremely small size. In contrast to known narrow capillarycolumns, the inner surface of which is wetted by a liquid, the passageof the fluid through the column 22 of the present invention takes placein such a fashion that the velocity distribution is not the sameeverywhere because the fluid has to stream around the irregularlyarranged and irregularly formed particles of the filling.

Because of the large particle size there is, in efiect, a series of openregions connected by narrow passages around the particles. This createsincreased velocity flow through the respective connecting passagesbetween the particles, as illustrated by the arrows in FIG. 2, butresults in a reduced flow velocity in the open regions between theparticles. It is believed that this type of flow has the effect ofcontinually mixing the fluids along a relatively narrow front andincreases the separation power of the column. The mixing effect in therather large open regions between the particles seems to overcome anytendency for the fluid sample to spread due to increased velocity flowthrough one portion of the tube over that of another.

By using a method to be hereinafter described, a small diameter columnwas packed with particles ranging from /3 to /2 of the diameter of thecolumn. This column had a length of 2 meters and an inner diameter of 4mm. In order to demonstrate the ability of such a column as employed ina gas chromatograph system, there is shown, in FIG. 3, a chromatogramillustrating the separation of a number of hydrocarbons in a gasmixture. This separation took place in 20 seconds. Peak 1 corresponds tomethane, peak 2 to ethane and peak 3 to ethylene. Peaks 4, 5, 6 and 7correspond respectively to propane, propylene, isobutane and the normalbutane. The chromatogram was made with the column maintained 'at atemperature of 90 C. Hydrogen was'used as the carrier gas and thepressure of the gas at the column entry was 3 atmospheres. Note thatthis column separated the components so completely as to result in baseline resolution for each component. That is, each peak was suflicientlyseparated from the next so that the recording instrument approached thebase line 9 before another component began to pass through the detectorand to afiect the movement of the recorder. With such a resolution ofcomponents the peak heights provide an accurate represent-ation of thepercentage of the respective components within the sample at constantoperating conditions.

It is found that a column packed in accordance with traditionalconcepts, having a much larger diameter and using small particles, i.e.,particles much less than /5 of the inner diameter of the column, andhaving a length of 2 meters, provides much more resistance to fluid flowand greatly reduced the linear speed of the carrier gas during a similarchromatographic analysis at a pressure of 3 atmospheres. A chromatogram,similar to that of FIG. 3, made with a classical type column in a gaschromatograph system would take from 3 to 4 minutes at a pressure of 3atmospheres. Thus, a column having the particle-to-tube size ratio ofthe present invention, when used in a gas chromatograph system, is from8 to 10 times faster than the conventional gas chromatograph column atthe same pressures with equally good resolution.

It has been found that a departure from the normally accepted practiceof using particles smaller than ,6 of the diameter of the tube to a useof particles /5 or more of the diameter of the tube produces a dnamaticand unexpected benefit in the form of high column efliciency at lowpressure drop (high permeability).

As applied to gas chromatograph columns, the effect is most clearly seenin the graph shown in FIG. 8. Here the dimensionless quantities B /H andB /d are shown as functions of the tube-to-particle diameter natio, D/d, where D is the diameter of the column and d is the diameter of thepacking particles. B the specific permeability coefiicient, is inverselyproportional to the pressure drop required per unit length of column perunit of linear velocity. H is the maximum height equivalent to atheoretical plate (at the optimum linear gas velocity) and is the ratioof the column length to the optimum number .of theoretical platesobtained. The dimensionless quantity B lH is thus proportional to thetheoretical I plate number, squared, per unit of pressure drop and perunit length of column; hence B /H is proportional to the product of thenumber of plates per unit length and the number of plates per unit ofpressure drop at fixed linear gas velocity (columns of differentdiameter are appropriately compared at fixed linear velocity rather thanfixed volume flow rate, since both the relative plate efiicieucy and theanalysis time tend to be companable for different columns operated atfixed linear velocity). Since the largest possible number of plates isdesired at the lowest possible pressure drop and for the shortestpossible column, B /H is clearly a figure of merit for columnperformance.

The dimensionless function B /d is a specific permeability which hasbeen corrected for the direct influence of particle size and thusmeasures only those changes in the permeability resulting fromincreasing porosity as D/ d is decreased. The observed form of thisfunction was as expected from the known Kozeny-Carman equation. However,the significant departure of the curve for B /H from the curve for 3 /11in the range of D/d below approximately 5:1 is unexpected and completelycontrary to prior art thinking.

The figure of merit B /l l is seen to be strikingly high for values ofD/ d below about 5 (i.e., for particles greater than about /5 of thecolumn diameter). The use of such ratios with the column dimensionsnormally employed was previously considered undesirable because of thebelief that small, uniformly packed particles were required for goodplate efliciency. Since present-day measuring techniques for plateheight still involve appreciable experimental error, except when extremeprecautions are taken, and since measurements on fragile particles suchas firebrick may tend to include :a range of mixed mesh column diameterratios of or greater.

Note, in FIG. 8, that the figure of merit B /H goes to a distinctmaximum or peak at a value of D/d between 3 and 2 and then diminishesrapidly at lower values of D/d, since the permeability must, obviously,go to zero when the particle diameter equals the tube diameter (i.e.,where D/d equals 1). However, it will also be noted that the improvedperformance associated with large particle-to-tube diameter ratio isobserved almost up to the limiting particle-to-tube diameter ratio ofunity.

It will be understood that, while the column shown in FIG. 2 is of thegas-solid type, in which the packing particles themselves comprise thesorptive material, the present invention is also applicable togas-liquid type chromatographic columns. That is, the same generalprinciples apply with regard to particle size and the tube diameter ingas-liquid chromatography with the particles providing support for athin layer of partitioning liquid which causes the separation as the gasmixture flows thereover.

It will also be understood that the column of the present invention isalso applicable to liquid-solid type chromatograph columns in which aliquid solution is used.

strongly adherent layer of partioning liquid which causes i a separationof the liquid sample carried in a liquid carrier solution. columns, itis found that the inner dimension :of the tube or column, according tothe invention, may be as large as 2 mm. in diameter. In general,however, an inner diameter of 1 mm. will sufiice, contrasting with thediameter of 0.25 mm. or smaller which is preferably the dimension ofcolumns of this construction as employed in gas chromatography. In bothgas and liquid type columns, the diameter of the patricles employedto-pack the columns are from /5 to /2 of the inner diameter of thecolumn and the quantity and volume of the particles In the case ofliquid chromatograph,

packed therein are such that they produce an inner-parformed. As shownschematically in FIG. 4, the column 22a may then be drawn down through asuitable die 26 to the desired diameter, with the particles 24a therein.

While the use of a die is shown in FIG. 4, it is well known that glasstubing may be drawn down without a die to a very small diameter. Forexample, a glass tube having an inner diameter somewhat larger than 2mm.was loosely packed with particles ranging between .1 and .15 mm. anddrawn out to a length wherein the inner diameter was reduced to .3 mm.This column is illustrated in greatly magnified cross section in FIG. 5.The

particles 24b within the resulting elongated tubing 22b have arrangedthemselves, in the drawing out process, into groups or clusters ofseveral particles separated by relatively short gaps or open spaces 23in turn connected {by narrow channels or passages (illustrated by thearrows in FIG. 5) around the particles. As may be seen in FIG. 5, thelength of the open spaces or gaps between adjacent clusters of particlesis between 1 to 5 times the cross-sectional dimension .of the particles.The open be drawn down to smaller diameters.

8 regions or gaps '23 have no deleterious efiect on the columnperformance. Because of the size of the particles, all of the openspaces or gaps are actually in the fluid stream and there are no sidedead volumes where the sample may hang up or spread. When used in gaschromatograph type analyses, the spaces 23 and passages of the columneifect a continual compression and dilitation of the gas stream and itis believed that this particle structure aids rather than hinders themass transfer between the gas and the absorbent particles. In drawingout glass columns the sidewalls of the columns become somewhat softenedand a few of the particles slightly imbed themselves in the wall of thecolumn. This actually lends support to the packing structure within theglass 1 column with the imbedded particles supporting those particlesloosely retained within the column.

However, the invention is not limited to tubes of glass,

butmay also be applied to other tubes such as copper,

stainless steel, aluminum or other meta-l tubes that may There are alsoplastic materials that can "be deformed at room temperatures or onlyslightly above room temperature-and these offer special advantages whenthe filling material cannot be heated.

In the construction of small diameter columns, such as those having aninner diameter less than 1 mm., where:

the column is formed by drawing the column down from a larger diameter,it is sometimes desirable to pack the particles as loosely as possibleto prevent the particles from binding during the drawing out process. Inpractice, such a loose packing may be accomplishedimerely by looselyfilling (without agitation or knocking) the larger size tube (2 to 4mm.) with relatively large size particles, i.e., with particles having adiameter at least /5 of. the

diameter of the column ultimately to be formed. Another.

wire 28 is extracted from the tube 220 while the tube is in thehorizontal position, leaving an unpacked space having the dimensions ofthe rod orwire for the length of the i The extra volume of the rodproduces a loosely tube. packed column that is still substantiallyevenly packed throughout the length of the column. prevents binding ofthe particles when the tube 220 is drawn to its desired size.

Columns to be employed for liquid chromatography are formed insubstantially the same manner as the columns used for gaschromatography, with the exception that the maximum inner diameter ofthe liquid chromatograph column in its completed form is preferablysomewhat larger than those columns to be employed for gaschromatography.

While in accordance with the Patent Statutes there has been describedwhat at present are'considered to be the. preferred embodiments of theinvention, it will be obvious to those skilled in the art that variouschanges and modifications may be made thereinwithout departing from theinvention and it is, therefore, the aim of the. appended claims to coverall such changes and modifications as fall within the true spirit andscope of the invention.

What is claimed is: I 1. A chromatographic column for the separation ofthe components of a mixture of gases, liquids or vapors flowingtherethrough comprising:

a tubular chromatographic column, and a packing of granular partitioningmaterial within the interior volume of said column, said individualgrains of said partitioning material supporting each other across thecross-section of said column and having sufiicient size to create in apacking thereof a re-. sultant inter-particle voi-d space of .at 'least45 per.-'

cent of the total packed volume of said column. 2. A chromatographcolumn for the separation of the This extra space 9 components of amixture of gases, liquids or vapors flowing therethrough comprising:

a tubular chromatographic column,

a packing of granular material within the interior volume of saidcolumn, said individual grains of said packing material supporting eachother across the cross-section of said column and having sufiicient sizeto create in a packing thereof, .a resultant interparticle void space ofat least 45 percent of the total packed volume of said column, and

a partitioning liquid coated on the surface of said granular particlesfor separating components of a gas stream flowing through said voidspace around said particles.

3. A chromatographic column for the separation of the components of amixture of gases, liquids or vapors flowing therethrough comprising:

a tubular chromatographic column, and

granular partitioning material packed Within the interior volume of saidcolumn, said individual grains of said partitioning material supportingeach other across the cross section of said column and having adimension greater than /5 of the inner diameter of said column.

4. A chromatographic column for the separation of the components of amixture of gases or vapors flowing therethrough comprising:

a tubular chromatographic column having an inner diameter less than 1mm., and

granular partitioning material packed within the interior volume of saidcolumn, said individual grains of said partitioning material supportingeach other across the cross-section of said column and having adimension larger than /5 of the inner diameter of said column.

5. A chromatographic column tor the separation of the components of amixture of gases or vapors flowing therethrough comprising:

a tubular chromatographic column having an inner diameter less than 1mm.,

a granular support material packed within the interior volume of saidcolumn, said individual grains of said support material supporting eachother across the cross-section of said column and having suflicient sizeto create in a packing thereof a resultant interparticle void space ofat least 45 percent of the total packed volume of said column, and

a partitioning liquid coated on the surface of said granular particlesfor separating components of a gas stream flowing through said voidspace around said particles.

6. A chromatographic column for the separation of the components of amixture of gases or vapors flowing therethrough comprising:

a tubular chromatographic column having an inner diameter :less than 1mm., and

10 granular partitioning material packed within said inner volume ofsaid column, said individual grains of said partitioning materialsupporting each other across the cross-section of said column and havinga dimension larger than /5 of the inner diameter of said column, thetotal volume of said solid granular material comprising :less thanpercent of the inner volume of the packed portion of said column.

7. A chromatographic column for the separation of the components of amixture of gases, liquids or vapors flowing therethr-ough comprising:

a tubular chromatographic column, and

a packing of granular material within said column, the

individual grains of said packing material having a cross-sectionaldimension greater than /5 of the inner diameter of said column, saidpacking being arranged within said column in small clusters of grains ofpacking material extending across said column separated by short spacestherebetween.

8. A chromatographic column for the separation of the components of amixture of gases, liquids or vapors flowing therethrou-gh comprising:

a tubular chromatographic column, and

granular partitioning material packed within said inner volume of saidcolumn, said individual grains of said partitioning material supportingeach other across the cross-section of ,said column and having adimension [larger than /5 of the inner diameter of said column, some ofsaid granular particles being imbedded into the side wall of said columnand supporting the remaining particles loosely retained within saidcolumn.

9. A chromatographic column for the separation of the components of amixture of liquid constituents comprismg:

a tubular chromatographic column having an interior diameter not greaterthan 2 mm., and

granular partitioning material packed within the interior volume of saidcolumn, said individual grains of said partitioning material supportingeach other across the cross-section of said column and having adimension larger than /5 of the inner diameter of said column.

References Cited by the Examiner UNITED STATES PATENTS 343,369 6/1886Haficke 55-387 X 1,654,925 1/ 1928 Dragler 55387 X 2,325,061 7/1943Kaufman 55388 X 3,005,514 10/1961 Cole et a1. 55-886 3,050,920 8/ 1962Norton.

3,170,969 2/1965 Lerner et al. 55-524 X 3,182,394 5/1965 Jentzsch55-=386 X REUBEN FRIEDMAN, Primary Examiner.

C. N. HART, Assistant Examiner.

